title: Longitudinal prostate-specific antigen reference ranges: Choosing the underlying model of age-related changes.
abstract: Serial measurements of prostate-specific antigen (PSA) are used as a biomarker for men diagnosed with prostate cancer following an active monitoring programme. Distinguishing pathological changes from natural age-related changes is not straightforward. Here, we compare four approaches to modelling age-related change in PSA with the aim of developing reference ranges for repeated measures of PSA. A suitable model for PSA reference ranges must satisfy two criteria. First, it must offer an accurate description of the trend of PSA on average and in individuals. Second, it must be able to make accurate predictions about new PSA observations for an individual and about the entire PSA trajectory for a new individual.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK andrew.simpkin@bristol.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpkin
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.affiliation: John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: Cambridge Research Institute Cancer Research, Cambridge, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D012016:Reference Values
chemical_list: D017430:Prostate-Specific Antigen
keywords: fractional polynomials; functional principal components; linear mixed models; longitudinal data; prostate-specific antigen; regression splines